An active ingredient from the combination of Corydalis Rhizoma and Paeoniae Radix Alba relieves chronic compression injury-induced pain in rats by ameliorating AR/Mboat2-mediated ferroptosis in spinal cord neurons

IntroductionA combination of Corydalis Rhizoma (the dried tuber of Corydalis yanhusuo W.T. Wang) and Paeoniae Radix Alba (the root of Paeonia lactiflora Pall.) has been traditionally employed for analgesia. However, the underlying pharmacological mechanisms have not been clarified. The aim of the pr...

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Main Authors: Ze-Ming Wang, Xiao-Hong Wei, Gui-Yang Xia, Lin-Nan Zhou, Jin-Yu Li, Sheng Lin
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1558916/full
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author Ze-Ming Wang
Xiao-Hong Wei
Gui-Yang Xia
Lin-Nan Zhou
Jin-Yu Li
Sheng Lin
author_facet Ze-Ming Wang
Xiao-Hong Wei
Gui-Yang Xia
Lin-Nan Zhou
Jin-Yu Li
Sheng Lin
author_sort Ze-Ming Wang
collection DOAJ
description IntroductionA combination of Corydalis Rhizoma (the dried tuber of Corydalis yanhusuo W.T. Wang) and Paeoniae Radix Alba (the root of Paeonia lactiflora Pall.) has been traditionally employed for analgesia. However, the underlying pharmacological mechanisms have not been clarified. The aim of the present study was to investigate the anti-inflammatory and analgesic effects of YB60, the 60% ethanol elution fraction derived from the combination of Corydalis Rhizoma and Paeoniae Radix Alba, and the explore the underlying mechanism.MethodsLipopolysaccharide-induced cellular inflammation model and chronic compression injury (CCI) rat model were used to study the anti-inflammatory and analgesic effects of YB60. Proteomics and molecular biology experiments were applied to explore the potential analgesic mechanism of YB60.ResultsThe results demonstrated that YB60 significantly decreased inflammatory cytokine levels both in cellular models and rat serum, while concurrently elevating pain thresholds in CCI rats. Proteomic analysis indicated that YB60 could upregulate the expression of Membrane Bound O-Acyltransferase Domain Containing 2 (Mboat2), a newly confirmed marker of ferroptosis. Furthermore, YB60 prevented ferroptosis in the spinal cords of CCI rats. Western blotting and immunofluorescent dual staining further revealed that YB60 increased the expression of Mboat2 and its upstream signaling molecule Androgen receptor (AR). Results in PC12 cells in vitro showed that YB60 reversed the downregulation of AR and Mboat2, and ameliorated ferroptosis induced by Erastin, while knockdown of AR eliminated the above effects of YB60.ConclusionThese findings indicated that YB60 exerted its analgesic effect by inhibiting ferroptosis in spinal cord neurons via modulation of the AR/Mboat2 pathway.
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spelling doaj-art-b4910edfbb894dd8acc855187bb73e5b2025-08-20T02:42:00ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15589161558916An active ingredient from the combination of Corydalis Rhizoma and Paeoniae Radix Alba relieves chronic compression injury-induced pain in rats by ameliorating AR/Mboat2-mediated ferroptosis in spinal cord neuronsZe-Ming Wang0Xiao-Hong Wei1Gui-Yang Xia2Lin-Nan Zhou3Jin-Yu Li4Sheng Lin5School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, ChinaKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, ChinaKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaIntroductionA combination of Corydalis Rhizoma (the dried tuber of Corydalis yanhusuo W.T. Wang) and Paeoniae Radix Alba (the root of Paeonia lactiflora Pall.) has been traditionally employed for analgesia. However, the underlying pharmacological mechanisms have not been clarified. The aim of the present study was to investigate the anti-inflammatory and analgesic effects of YB60, the 60% ethanol elution fraction derived from the combination of Corydalis Rhizoma and Paeoniae Radix Alba, and the explore the underlying mechanism.MethodsLipopolysaccharide-induced cellular inflammation model and chronic compression injury (CCI) rat model were used to study the anti-inflammatory and analgesic effects of YB60. Proteomics and molecular biology experiments were applied to explore the potential analgesic mechanism of YB60.ResultsThe results demonstrated that YB60 significantly decreased inflammatory cytokine levels both in cellular models and rat serum, while concurrently elevating pain thresholds in CCI rats. Proteomic analysis indicated that YB60 could upregulate the expression of Membrane Bound O-Acyltransferase Domain Containing 2 (Mboat2), a newly confirmed marker of ferroptosis. Furthermore, YB60 prevented ferroptosis in the spinal cords of CCI rats. Western blotting and immunofluorescent dual staining further revealed that YB60 increased the expression of Mboat2 and its upstream signaling molecule Androgen receptor (AR). Results in PC12 cells in vitro showed that YB60 reversed the downregulation of AR and Mboat2, and ameliorated ferroptosis induced by Erastin, while knockdown of AR eliminated the above effects of YB60.ConclusionThese findings indicated that YB60 exerted its analgesic effect by inhibiting ferroptosis in spinal cord neurons via modulation of the AR/Mboat2 pathway.https://www.frontiersin.org/articles/10.3389/fphar.2025.1558916/fullchronic painchronic compression injuryferroptosisARMboat2extract of Corydalis Rhizoma and Paeoniae Radix Alba
spellingShingle Ze-Ming Wang
Xiao-Hong Wei
Gui-Yang Xia
Lin-Nan Zhou
Jin-Yu Li
Sheng Lin
An active ingredient from the combination of Corydalis Rhizoma and Paeoniae Radix Alba relieves chronic compression injury-induced pain in rats by ameliorating AR/Mboat2-mediated ferroptosis in spinal cord neurons
Frontiers in Pharmacology
chronic pain
chronic compression injury
ferroptosis
AR
Mboat2
extract of Corydalis Rhizoma and Paeoniae Radix Alba
title An active ingredient from the combination of Corydalis Rhizoma and Paeoniae Radix Alba relieves chronic compression injury-induced pain in rats by ameliorating AR/Mboat2-mediated ferroptosis in spinal cord neurons
title_full An active ingredient from the combination of Corydalis Rhizoma and Paeoniae Radix Alba relieves chronic compression injury-induced pain in rats by ameliorating AR/Mboat2-mediated ferroptosis in spinal cord neurons
title_fullStr An active ingredient from the combination of Corydalis Rhizoma and Paeoniae Radix Alba relieves chronic compression injury-induced pain in rats by ameliorating AR/Mboat2-mediated ferroptosis in spinal cord neurons
title_full_unstemmed An active ingredient from the combination of Corydalis Rhizoma and Paeoniae Radix Alba relieves chronic compression injury-induced pain in rats by ameliorating AR/Mboat2-mediated ferroptosis in spinal cord neurons
title_short An active ingredient from the combination of Corydalis Rhizoma and Paeoniae Radix Alba relieves chronic compression injury-induced pain in rats by ameliorating AR/Mboat2-mediated ferroptosis in spinal cord neurons
title_sort active ingredient from the combination of corydalis rhizoma and paeoniae radix alba relieves chronic compression injury induced pain in rats by ameliorating ar mboat2 mediated ferroptosis in spinal cord neurons
topic chronic pain
chronic compression injury
ferroptosis
AR
Mboat2
extract of Corydalis Rhizoma and Paeoniae Radix Alba
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1558916/full
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